H2S is emerging as an important mediator of human physiology and pathology, but remains difficult to study due to the lack of methods to detect this gaseous signaling molecule in living systems in real time. H2S is a member of a family of endogenously produced reactive sulfur species (RSS) that includes thiols,i,ii S-nitrosothiols,iii sulfenic acids,iv and sulfite,v and plays vital roles in the regulation of intracellular redox states,vi as well as other fundamental signaling pathways involved in human health and disease.vii Like other gaseous signaling molecules nitric oxide (NO) and carbon monoxide (CO), H2S can interact directly with proteins, both by post-translationally modifying cysteine residues via sulfhydration,viii as well as by binding to the iron center in heme groups.ix H2S is important in many physiological processes including vasodilation,x angiogenesis,xi oxygen sensing,xii apoptosis,xiii inflammation,xiv and neuromodulation,xv and can protect against ischemia/reperfusion injury.xvi Furthermore, H2S levels are altered in a number of disease states including Alzheimer's disease,xvii Down's syndrome,xviii diabetes,xix and cirrhosis of the liver.xx Given this dichotomy between health and pathology, new methods to directly monitor the production and trafficking of H2S in living systems are urgently needed and would contribute to a deeper understanding of the role this species plays in human biology.
Current methods for H2S detection including colorimetric assays,xxi,xxii,xxiii electrochemical detection,xxiv gas chromatography techniques,xxv and metal-induced precipitation of sulfide,xxvi depend acutely on the precise procedures used for the processing of tissues or cell lysates and yield variable estimates of endogenous H2S that range from nM to high μM.xxv,xxvii,xxviii Our invention provides a general solution to this and other problems.